Analysis of proliferation and apoptotic induction by 20 steroid glycosides in 143B osteosarcoma cells <i>in vitro</i>

Delebinski, Catharina I.; Georgi, Sean; Kleinsimon, Susann; Twardziok, Monika; Kopp, Brigitte; Melzig, Matthias F.; Seifert, Georg

doi:10.1111/cpr.12208

Cited by 17 publications

(15 citation statements)

References 73 publications

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“…Indeed, this class of molecules is highly represented in the top hits of our screens, with members demonstrating variable levels of potency and selectivity. Proscillaridin A itself has been previously identified in screens for anti-neoplastic compounds against glioblastoma, osteosarcoma and colon cancer cell lines ( 37 – 39 ). The reason(s) underlying Proscillaridin A’s selectivity towards KRAS mutated tumor cells in the 3D spheroid format are unclear.…”

Section: Discussionmentioning

confidence: 99%

A novel three-dimensional high-throughput screening approach identifies inducers of a mutant KRAS selective lethal phenotype

et al. 2018

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The RAS proteins are the most frequently mutated oncogenes in cancer, with highest frequency found in pancreatic, lung, and colon tumors. Moreover, the activity of RAS is required for the proliferation and/or survival of these tumor cells and thus represents a high-value target for therapeutic development. Direct targeting of RAS has proven challenging for multiple reasons stemming from the biology of the protein, the complexity of downstream effector pathways and upstream regulatory networks. Thus, significant efforts have been directed at identifying downstream targets on which RAS is dependent. These efforts have proven challenging, in part due to confounding factors such as reliance on two-dimensional adherent monolayer cell cultures that inadequately recapitulate the physiologic context to which cells are exposed in vivo. To overcome these issues, we implemented a High Throughput Screening (HTS) approach using a spheroid-based 3-dimensional culture format, thought to more closely reflect conditions experienced by cells in vivo. Using isogenic cell pairs, differing in the status of KRAS, we identified Proscillaridin A as a selective inhibitor of cells harboring the oncogenic KRasG12V allele. Significantly, the identification of Proscillaridin A was facilitated by the 3D screening platform and would not have been discovered employing standard 2D culturing methods.

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Section: Discussionmentioning

confidence: 99%

A novel three-dimensional high-throughput screening approach identifies inducers of a mutant KRAS selective lethal phenotype

et al. 2018

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“…Osteosarcoma, the most common bone malignancy, is the major cause of tumor‐associated death in adolescents and children . Osteosarcoma is characterized by osteoblastic differentiation and malignant osteoid production and early symptoms of osteosarcoma are nonspecific .…”

Section: Introductionmentioning

confidence: 99%

LncRNA Linc00511 promotes osteosarcoma cell proliferation and migration through sponging miR‐765

Liu

et al. 2018

J of Cellular Biochemistry

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Long noncoding RNA (lncRNA) Linc00511 is a novel lncRNA, and it was reported to play important roles in the progression and carcinogenesis of several tumors. However, the expression and biological roles of Linc00511 in osteosarcoma were still unknown. In this research, we showed that the expression of Linc00511 was upregulated in osteosarcoma samples and cell lines. Ectopic expression of Linc00511 promoted osteosarcoma cell growth, colony formation, and migration. Moreover, overexpression of Linc00511 enhanced the epithelial‐mesenchymal transition progression in osteosarcoma cell. In addition, we showed that elevated expression of Linc00511 suppressed microRNA‐765 (miR‐765) expression and promoted apurinic/apyrimidinic endonuclease 1 (APE1) expression in osteosarcoma cell. The expression of miR‐765 was downregulated in osteosarcoma cells and samples and was negatively related to Linc00511 expression in osteosarcoma tissues. Ectopic expression of miR‐765 inhibited osteosarcoma cell growth and migration. Furthermore, we showed that Linc00511 overexpression promoted MG‐63 cells proliferation, colony formation, and migration via downregulation of miR‐765. These results suggested that Linc00511 played as an oncogene in the development of osteosarcoma.

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“…*p < 0.05; **p < 0.01; ***p < 0.001 compared to control groups. tion of apoptosis in cancer cells (Delebinski et al, 2015). Accordingly, we explored whether the growth inhibitory effect of STA was related to apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Stephanthraniline A suppresses proliferation of HCT116 human colon cancer cells through induction of caspase-dependent apoptosis, dysregulation of mitochondrial function, cell cycle arrest and regulation of Akt/p38 signaling pathways

Wang

Yao

et al. 2019

J. Toxicol. Sci.

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-Stephanthraniline A (STA) is a C 21 steroidal aglycone isolated from the stem of Stephanotis mucronata (Blanco) Merr. that exerts growth inhibition in human colon cancer cells. However, the intracellular molecular mechanisms whereby this occurs have not been well characterized. In this study, we found that STA significantly inhibits the growth of HCT116 colon cancer cells in a time-and concentration-dependent manner. The inhibitory effect of STA on cell growth was related to the induction of apoptosis. Activated caspase-3, caspase-8 and caspase-9, along with a decreased Bcl-2/Bcl-x ratio and loss of mitochondrial membrane potential (Δψ m), were observed in response to STA treatment. Furthermore, treatment of HCT116 cells with STA resulted in G0/G1 phase cell cycle arrest accompanied by decreased mRNA levels of cyclin-dependent kinase 4 (CDK4), p21 and c-myc. Additionally, the inhibition of Akt signaling and activation of p38 signaling were observed after treatment with STA in HCT116 cells. These findings indicate that STA inhibits HCT116 cell growth by promoting apoptosis, the dysregulation of mitochondrial function, and cell cycle arrest.

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Analysis of proliferation and apoptotic induction by 20 steroid glycosides in 143B osteosarcoma cells in vitro

Abstract: These results indicate that bufadienolides proscillaridin A and arenobufagin and cardenolide evomonoside, or related natural compounds might be promising new starting points for development of novel anti-cancer agents for treatment of osteosarcoma.

Cited by 17 publications

References 73 publications

A novel three-dimensional high-throughput screening approach identifies inducers of a mutant KRAS selective lethal phenotype

A novel three-dimensional high-throughput screening approach identifies inducers of a mutant KRAS selective lethal phenotype

LncRNA Linc00511 promotes osteosarcoma cell proliferation and migration through sponging miR‐765

Stephanthraniline A suppresses proliferation of HCT116 human colon cancer cells through induction of caspase-dependent apoptosis, dysregulation of mitochondrial function, cell cycle arrest and regulation of Akt/p38 signaling pathways

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